Allergy Asthma Immunol Res.  2011 Apr;3(2):123-127. 10.4168/aair.2011.3.2.123.

Role of Toll-like Receptor 3 Variants in Aspirin-Exacerbated Respiratory Disease

• Palikhe NS
• Kim SH
• Kim JH
• Losol P
• Ye YM
• Park HS

• KMID: 2130364
• DOI: http://doi.org/10.4168/aair.2011.3.2.123

Abstract

PURPOSE
Although the mechanism of virus-induced, aspirin-exacerbated respiratory disease (AERD) is not known fully, direct activation of viral components through Toll-like receptor 3 (TLR3) has been suggested. TLR3 recognizes double-stranded RNA (dsRNA), and activates nuclear factor-kappaB and increases interferon-gamma, which signals other cells to induce airway inflammation in asthma. Considering the association of TLR3 in viral infections and AERD, we investigated whether promoter and non-synonymous variants of TLR3 were associated with AERD.
METHODS
The three study groups, 203 with AERD, 254 with aspirin-tolerant asthma (ATA), and 274 normal healthy controls (NC) were recruited from Ajou University Hospital, Korea. Two polymorphisms, -299698G>T and 293391G>A [Leu412Phe], were genotyped using primer extension methods.
RESULTS
Genetic associations were examined between two genetic polymorphisms of TLR3 (-299698G>T and 293391G>A [Leu412Phe]) in the three study groups. AERD patients that carried the GG genotype of 293391G>A showed a significantly lower frequency compared with ATA in both co-dominant (P=0.025) and dominant models (P=0.036). Similarly, in the minor allele frequency, the A allele was significantly higher (P=0.023) in AERD compared with ATA for this polymorphism. AERD patients who carried HT2 [GA] showed a significantly higher frequency than other haplotypes in co-dominant (P=0.02) and recessive (P=0.026) models.
CONCLUSIONS
Our findings suggest that the -299698G>T and 293391G>A [Leu412Phe] polymorphisms of the TLR3 gene are associated with the AERD phenotype.

Keyword

TLR3 polymorphism; aspirin sensitivity; asthma; viral infection

MeSH Terms

Alleles
Asthma
Gene Frequency
Genotype
Haplotypes
Humans
Inflammation
Interferon-gamma
Korea
Phenotype
Polymorphism, Genetic
RNA, Double-Stranded
Toll-Like Receptor 3
Toll-Like Receptors
Viral Structures
Interferon-gamma
RNA, Double-Stranded
Toll-Like Receptor 3
Toll-Like Receptors

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